The overall goal for this investigation is to develop a cannabinoid type drug(s) which has immunosuppressant activity particularly aimed at the thymus (T) dependent lymphocyte which is devoid or possesses minimal psychotropic action. We have performed structure-activities studies and have narrowed the structure to 2 types. Our objective for this grant period is to study 1-methoxy 8,9-epoxy hexahydrocannabinol and a flourinated cannabidiol. Both of these compounds are provided by Dr. Raj Razdan of the Sheehen Institute, Cambridge, Mass. Emphasis will be placed on the T lymphocyte as the target cell and the bone marrow as the potential site of toxicity. Detailed mechanistic studies will be performed and compared to the parent compounds. The development of a specific T cell suppressant will be most useful in such clinical situations as organ transplantation, bone marrow transplantation as well as in a number of autoimmune diseases caused by cell mediated immunity. The cannabinoids may offer such a drug which could be used in these diseases and which have adverse effects. BIBLIOGRAPHIC REFERENCES: Levy, J.A. and Munson, A.E.: Suppression of antibody mediated primary hemolytic plaque forming cells (PFC) by haloperidol. Fed. Proc. 1976, 35: 713, 1976. Smith, S.H., Sanders, V.M., and Munson, A.E.: Immunosuppressant activity of Delta 8-tetrahydrocannabinol (Delta 8-THC) and congeners. J. Reticuloendothelial Soc. 20: 50a, 1976.